The themes of the Indiana Alcohol Research Center (IARC) renewal Genetics of Alcoholism and Responses to Alcohol are to identify correlates between risk factors (e.g., a positive family history of alcohol use disorders (AUD), externalizing behaviors (including different forms of impulsive behavior), patterns of binge drinking, and GABRA2 alleles) and: 1) measures of craving alcohol (assessed by operant work for alcohol using paradigms we have developed for both animals and humans), and 2) brain responses to novel cues conditioned to alcohol intoxication. Our aims will advance NIAAA's goal of identifying the physiological traits of alcohol risk endophenotypes. We will extend our knowledge of the basis for alcohol preference in rats by sequencing the genomes of P/NP and HAD/LAD rats and defining the sequences resulting from selective breeding. With these complementary, parallel investigations, our Center fulfills a critical need to integrate human and animal studies of how risk genes affect responses and endophenotypes related to AUDs. The rationale for continuing our Center is that: 1) by working in close association across scientific disciplines spanning behavioral neuroscience, neuroanatomy, molecular biology, genetics, genomics, biochemistry, neurobiology, and bioinformatics, our investigators can achieve insights that are not possible when working in isolation, 2) the Center has made unique contributions to alcoholism research and dissemination of resources around the world, 3) it combines human and animal studies examining overlapping risk factors for AUDs, and 4) it provides an unparalleled multi-disciplinary training environment for students, fellows, and young faculty. The expected outcome of our combined work, in toto, is a far greater understanding of the relationship between genetic and behavioral risk factors for AUDs, as well as the mechanisms through which these genetic factors act. The positive impact of such knowledge will be the ability to better target future prevention and treatment strategies, and to advance our understanding of factors influencing how the human brain governs the approach toward, consumption of, response to, and eventually dependence upon alcohol intoxication. These outcomes will be achieved through the activities and interactions of Administrative, Animal Production, and Genomics and Bioinformatics Cores, a Pilot Projects and Translational Research and Science Education Component, and five research Components: two carrying out cutting edge translational human research with alcohol infusion technology invented by IARC researchers, and three using animal models created and characterized by IARC investigators.